Journal of Psychiatry & Neuroscience最新文献

Background: Brain-derived neurotrophic factor (BDNF) is a key factor in neurodevelopment of autism spectrum disorder (ASD), yet the variability of peripheral BDNF levels in ASD remains debated. We sought to investigate the relationship between circulating oxidative stress and peripheral BDNF in children with ASD.

Methods: We analyzed plasma BDNF levels and redox status in both plasma and peripheral blood mononuclear cells (PBMCs) among children with ASD and typically developing (TD) children aged 2-5 years. We generated an autism-like mouse model via prenatal exposure to medroxyprogesterone acetate (MPA). To modulate circulating redox balance, we employed tyrosine kinase-driven lentiviral expression of superoxide dismutase 2 (Sod2) and hematopoietic stem cell (HSC) transplantation with Sod2 overexpression. We then assessed circulating redox balance, gene expression, epigenetic changes, peripheral BDNF levels, and autism-like behaviours in offspring.

Results: We included 78 children in the ASD group and 63 children in the TD group. Children with ASD exhibited elevated plasma BDNF levels and an altered redox balance compared with TD controls. In the mouse model, MPA-exposed autism-like offspring demonstrated increased peripheral BDNF levels and heightened oxidative stress in hematopoietic stem cells, endothelial cells, and PBMCs. Tyrosine kinase-Sod2 lentiviral expression in the endothelium fully normalized peripheral BDNF levels, while HSC transplantation with Sod2 overexpression not only reduced plasma BDNF levels, but also alleviated autism-like behaviours.

Limitations: This study's cross-sectional data limit causal inference between oxidative stress and BDNF levels among children with ASD. The mouse model, while informative, may not fully recapitulate human ASD heterogeneity.

Conclusion: In ASD, elevated peripheral BDNF levels are associated with circulating oxidative stress. Prenatal progestin exposure induces both increased peripheral BDNF and oxidative stress, effects that can be completely reversed through SOD2 modulation in circulation among mouse offspring.

Background: Both cerebral blood flow (CBF) and fractional anisotropy (FA) are altered in bipolar disorder (BD). We sought to investigate the unexplored CBF-FA association in relation to youth BD.

Methods: We recruited youth with BD, high-risk youth with a family history of BD, and healthy controls. Using 3 T magnetic resonance imaging, we measured global and regional grey matter CBF using arterial spin labelling and we measured regional FA using diffusion tensor imaging. We explored the CBF-FA association across groups, between groups, and by sex. Analyses of the BD group further examined mood effects. We conducted region-of-interest analyses of global CBF and FA, anterior cingulate cortex (ACC) CBF, and cingulate FA.

Results: We included 59 youth with BD, 19 high-risk youth with a family history of BD, and 47 healthy controls. There were no significant CBF-FA associations in the overall sample. Within the BD group, higher ACC CBF was associated with higher cingulum FA (β-weight 0.30, p = 0.03), with larger effect sizes among females and asymptomatic participants. Among controls, higher global CBF was associated with lower global FA (β-weight -0.40, p = 0.05). Within-sex analyses in the overall sample revealed a small effect size association between ACC CBF and cingulum FA among females only.

Limitations: Our small sample size limited power, and our cross-sectional observational design precluded directional inferences about CBF-FA associations.

Conclusion: We found preliminary evidence that ACC CBF was positively associated with cingulum FA among youth with BD, which may be driven by asymptomatic female participants. These associations may relate to differences in cerebral metabolism or white matter perfusion. Prospective and experimental studies are warranted to better understand CBF-FA associations in BD.

Stopping treatment with serotonin reuptake inhibitors (SRIs) often leads to withdrawal symptoms, which can be mitigated by a slow, hyperbolic taper using subtherapeutic dosage strengths. Unfortunately, conventional drug formularies lack the necessary breadth of dosing options to gradually wean SRIs, and alternative methods (e.g., bead counting, homemade dilutions, compounding) are difficult to implement for many patients. It has been suggested that fluoxetine, a widely available antidepressant with an unusually long elimination half-life, can help patients successfully discontinue SRIs, but the technique is poorly characterized. We propose a standardized fluoxetine substitution protocol that facilitates the discontinuation of compatible SRIs while minimizing adverse events.

Background: Mood disorders, including depressive and bipolar disorders, begin in late adolescence to early adulthood, tend to run in families, and present early with subthreshold symptoms. They have been associated with differential connectivity in 3 core networks: the default mode network (DMN), cognitive executive network (CEN), and salience network (SN), but it remains unclear whether differences in connectivity in the DMN, CEN, and SN are associated with familial risk for mood disorders.

Methods: We recruited youth aged 9-19 years, including offspring of parents with major depressive or bipolar disorders (familial high risk [FHR]) and offspring of parents with no mood disorder (controls) for a resting-state functional magnetic resonance imaging study. We tested associations between family history of major mood disorders and connectivity within and between the DMN, CEN, and SN.

Results: We included 215 youth: 126 at FHR with a mean age of 13.38 (standard deviation [SD] 2.91) years and 79 controls with a mean age of 13.17 (SD 2.67) years. Mean connectivity in the DMN (β = 0.003, 95% confidence interval [CI] -0.023 to 0.029), CEN (β = -0.009, 95% CI, -0.070 to 0.089), and SN (β = -0.010, 95% CI -0.071 to 0.051) in the FHR group was similar to that of controls. Moreover, DMN, CEN, and SN connectivity was not significantly associated with depressive symptoms.

Limitations: Given that brain connectivity changes over the developmental period, longitudinal studies would improve understanding of how this change occurs in familial risk groups to identify critical time periods for intervention or prevention of mood disorders.

Conclusion: Connectivity within and between the DMN, CEN, and SN is not a neural indicator of familial risk for major mood disorders.

Background: Numerous neuroimaging studies investigating the neural substrates of obsessive-compulsive disorder (OCD) have yielded inconsistent findings, and growing evidence suggests that psychiatric disorders are more accurately localized to brain networks rather than discrete brain regions. We sought to identify brain network localization in OCD.

Methods: We initially examined brain locations of structural and functional alterations among patients with OCD and healthy controls using neuroimaging studies. Employing a novel technique called functional connectivity network mapping (FCNM) and large-scale human brain connectome data, we mapped these damaged brain regions to 2 brain impairment networks in OCD.

Results: We included 62 neuroimaging studies involving 2578 patients with OCD and 2502 healthy controls. For FCNM, we used data from 556 healthy adults. Among patients with OCD, the grey matter volume (GMV) and resting-state activity impairment networks encompassed a broad range of brain regions, primarily involving the default mode, sensorimotor, and limbic networks, as well as the bilateral middle frontal gyrus and bilateral middle temporal gyrus. Additionally, the GMV impairment network specifically involved bilateral inferior frontal gyrus.

Limitations: We used large-scale human brain connectome data from healthy people, rather than the samples clinically and demographically matched to the original study participants, to examine brain networks in OCD.

Conclusion: Our study integrated an FCNM method with large-scale human brain connectome data to map heterogeneous abnormal brain locations of OCD to structural and functional impairment networks. Our findings deepen our understanding of the neuropathological mechanisms of OCD from a network perspective and may inform future neuromodulation treatment.

Background: Although it has been suggested that the hippocampus and amygdala (HA) are involved in the neurobiology of obsessive-compulsive disorder (OCD), volumetric findings have been inconsistent, and little work has been undertaken on the volumetry of the heterogeneous anatomic units of HA, with their specific functions and cytoarchitecture, in OCD. We sought to explore potential sources of heterogeneity in brain volumes by performing a separate analysis for people with and without psychotropic medication use, as well as the association of subfield volumes with OCD symptom severity.

Methods: We segmented T ₁-weighted images from people with OCD and healthy controls in the OCD Brain Imaging Consortium to produce 12 hippocampal subfields and 9 amygdala subfields using Free-Surfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age and quadratic effects of age, sex, site, and whole HA volume. We also performed subgroup analyses to examine subfield volume in relation to comorbid anxiety and depression, medication status, and symptom severity. We corrected all analyses for multiple comparisons using the false discovery rate (FDR).

Results: We included images from 381 people with OCD and 338 healthy controls. These groups did not significantly differ in HA subfield volumes. However, medicated people with OCD had significantly smaller volumes in the hippocampal dentate gyrus (p _FDR = 0.04, d = -0.26) and molecular layer (p _FDR = 0.04, d = -0.29), and larger volumes in the lateral (p _FDR = 0.049, d = 0.23) and basal (p _FDR = 0.049, d = 0.25) amygdala subfields, than healthy controls. Unmedicated people with OCD had significantly smaller volumes in the hippocampal cornu ammonis sector 1 (p _FDR = 0.02, d = -0.28) than controls. We did not detect associations between any subfield volume and OCD severity.

Limitations: We used cross-sectional data, which limits the interpretation of our analysis.

Conclusion: Differences in HA subfields between people with OCD and healthy controls are dependent on medication status, in line with previous work on other brain volumetric alterations in OCD. This emphasizes the importance of considering psychotropic medication in neuroimaging studies of OCD.